The dihydropteridinones of formula (I) according to the invention are an innovative new cytostatic active substance in the oncological treatment of fast-growing types of cancer. Usually, cytostatic medications are administered as parenteral preparations, even though their oral bioavailability may be perfectly adequate. The reason for this is that treatment with cytostatics is generally accompanied by a range of gastrointestinal side-effects which is frequently characterised by nausea, vomiting and/or diarrhoea, and consequently effective treatment by oral route would be jeopardised thereby.
These circumstances also apply to the dihydropteridinones of formula (I) and make it essential to prepare a solution for parenteral infusion or injection.
In the prior art EP 0219784 and WO 01/78732 describe methods of preparing and stabilising solutions for infusion containing ciprofloxacin by using one or more physiologically acceptable acid(s) of organic or inorganic origin. EP A 0287926 relates that the risk of particle formation can be greatly reduced by the use of highly pure grades of ciprofloxacin. EP 0143478 A1 describes the preparation of a stable hydrochloric acid solution of cisplatin, suitable for injection, which is particularly free from other additives. DE 197 03023 discloses that the stability of infusible solutions with regard to the formation of particulate impurities can be vastly improved by the use of glass containers with siliconised surfaces.
The aim of the present invention is to provide a stable infusible or injectable solution of dihydropteridinones of formula (I) for the desired dosage range tailored to treatment. As a further objective of the invention the stable infusible or injectable solution should be suitable both as a ready-to-use solution and as a concentrate for further dilution with solutions commonly used for parenteral administration such as for example isotonic NaCl solution, isotonic dextrose solution or Ringer lactate solution, to allow flexible adaptation of the dosage.